The research proposal is a combined basic and clinical investigation on the exactness of DNA synthesis in human lymphocytes. Our overall objective is to determine if malignant cells synthesize DNA with less accuracy than normal cells. We will measure the frequency by which incorrectly base-paired nucleotides are incorporated into polynucleotide templates using "nucleic acid-free extracts" from leukemic lymphocytes and from normal lymphocytes stimulated to divide by phytohemagglutinin. Our initial results indicate the nucleic-acid-free extracts from patients with acute leukemia incorporate dCTP into poly d(A-T) point poly d(A-T) 10-times more frequently than extracts from normal stimulated lymphocytes. Our objectives are: 1. To study the exactness of DNA synthesis with leukemic lymphocytes using different polynucleotide templates. 2. To isolate and purify DNA polymerase from leukemic lymphocytes to determine if a particular polymerase is responsible for the observed infidelity in DNA synthesis. 3. To determine if DNA synthesis is defective in patients with disease having a high incidence of leukemia.